1. Field of the Invention
The present invention relates to methods and apparatus for passively controlling fluid flow through microchannels. More specifically, the present invention relates to passive stopping means in a microfluidic circuit that act as pressure barriers to impede and direct the flow of fluid through microchannels, and methods for their use.
2. Description of Related Art
Controlling the movement of fluids through channels on a micro scale has important applications in a number of technologies. For example, in the field of molecular biology, polymerase chain reactions (PCR) have been performed in a chip containing microfabricated flow channels (U.S. Pat. Nos. 5,498,392; 5,587,128; 5,726,026). In the electronics field, thermal ink jet printers use printheads with microchannels through which ink must flow in a well-controlled manner (U.S. Pat. No. 5,119,116). Proper control of fluids through microchannels has been a challenge, because microdimensions impart characteristics and behaviors that are not found in larger scale systems, which are due primarily to the greater influence of surface effects.
The term xe2x80x9csurface effectsxe2x80x9d is used to describe specific characteristics of a surface on a micro scale. Materials often have unbound electrons, exposed polar molecules, or other molecular level features that generate a surface charge or reactivity characteristic. Due to scaling, these surface effects or surface forces are substantially more pronounced in microstructures than they are in traditionally sized devices. This is particularly true in micro scale fluid handling systems where the dynamics of fluid movement are governed by external pressures and by attractions and repulsions between liquids and the materials of the microfluidic systems through which they flow.
Many micro scale fluid handling systems suffer from uneven and irregular fluid flow. Many such problems are due to surface effects such as those mentioned above. It is frequently the case that microscale fluid handling systems are designed to perform multiple fluid handling steps in parallel. However, some microscale fluid systems fill unevenly. In others, channels fill at different rates. Additionally, some fluid circuits that split samples into multiple reaction chambers may do so unevenly. Those combining samples from multiple reaction chambers may do so incompletely or unevenly. Such problems may result in incomplete assays or assays conducted with insufficient amounts of reagent or sample. Some of these problems may result in differences in the reaction times for the different assays, thus changing the results. These and other problems may affect the accuracy of assays and the usability of the microscale fluid handling systems themselves.
Accordingly, a need becomes apparent for fluid circuits in which fluid flow may be regulated. Technologies for actively regulating the flow of fluid through fluid circuits are generally not favored due to their complexity and cost. Thus, a need specifically exists for fluid circuits that allow for the passive regulation of fluid flow internally. This could be accomplished by providing fluid circuits comprising passive stopping means for acting as pressure barriers to regulate the flow of fluid through microchannels. Such fluid circuits and methods for their use are disclosed herein.
The apparatus of the present invention has been developed in response to the present state of the art, and in particular, in response to the problems and needs in the art that have not yet been fully solved by currently available microscale fluid handling systems, also called microfluidics systems.
Thus, the present invention discloses means of controlling the flow of fluids through microchannels in a manner to allow mixing or diluting of the fluids and/or separation of the fluids or a fluid into several channels for multiprocessing. It also discloses various means for consolidating or combining several samples or channels into a smaller number of samples or channels, and the use of air escape channels and stopping means to facilitate complicated fluid processing. The flow of fluid through the microchannels is primarily controlled by structures that act as passive fluid flow barriers, which in the present invention are abrupt microchannel widenings purposely formed into the microchannels by micromachining or other manufacturing techniques. Abrupt microchannel widenings include short, low volume, widenings, i.e., a restricted region of a microchannel having an increased diameter, being short enough that the widening does not significantly increase the overall volume of the channel; longer widenings, as occur when a channel enters a well or chamber; step changes in channel diameter, i.e., points where a smaller diameter channel joins a larger diameter channel; and even points where a channel enters a substantially xe2x80x9cunboundedxe2x80x9d space, i.e., the channel opens to the exterior surface of the microfluidic device. These passive fluid flow barriers or abrupt microchannel widenings act to stop fluid flow by creating a passive pressure barrier that may be overcome by sufficient pressure, or by wetting both sides of the barrier. Passive fluid flow barriers can be produced by abrupt microchannel widenings in both hydrophilic and hydrophobic materials.
Unlike flow barriers that require moving parts, the passive fluid flow barriers or abrupt microchannel widenings can be static and their operation does not depend upon the use of moving parts. They are thus cheaper and simpler to construct than the various types of microelectromechanical active valves, and they do not require external controls.
Passive flow barriers formed by abrupt microchannel widenings may be used in microfluidic circuits in combination with other types of passive fluid flow barriers, which may include hydrophobic channel widenings, microchannel regions having modified surface properties (e.g., regions where the contact angle or the surface tension has been modified, e.g., by including films of salts or surfactants or by a hydrophobic patch in an otherwise hydrophilic channel, or vice versa).
These and other objects, features, and advantages of the present invention will become more fully apparent from the following description and appended claims, or may be learned by the practice of the invention as set forth hereinafter.